Omega-3 fatty acids have been used as treatments for schizophrenia with inconsistent results. In particular, studies thus far have used omega-3 treatments for patient groups with broad clinical characteristics, but this broad use may obscure omega-3 effects by including patients who may not ultimately benefit from such treatment. This study will provide the necessary groundwork for determining whether omega-3 treatment should be targeted to more selected patient populations. Erythrocyte membrane omega-3 concentration is a possible response marker given that it has been demonstrated to be abnormal in patients, reflects membrane phospholipid metabolism in the brain and has been linked to long-term outcome in early phase schizophrenia from our pilot data. Moreover, omega-3 fatty acids are essential components of cell membranes and supporting oligodendrocytes and play a critical role in myelination. Animal studies indicate that omega-3 fatty acid supplementation increases brain myelin. In-vivo diffusion tensor imaging (DTI) studies provide strong evidence for abnormalities in white matter integrity in patients with schizophrenia that are associated with worse symptom severity. Interestingly, pilot data from our group indicate that lower peripheral omega-3 concentration is associated with worse white matter integrity in patients, thus laying the groundwork for the proposed study. The specific aims of this study are to: (1) examine the efficacy of omega-3 fatty acids as an adjuvant agent in the treatment of patients with recent-onset schizophrenia; (2) identify whether pretreatment fractional anisotropy assessed by DTI predicts which patients will derive clinical benefit from omega-3 fatty acids; and (3) to identify whether pretreatment peripheral omega-3 fatty acid concentration predicts which patients will derive clinical benefit from omega-3 fatty acids. Exploratory aims included examining whether there is a differential effect of fractional anisotropy versus peripheral omega-3 concentration in predicting response to omega-3 supplementation. The main hypothesis to be tested in this study is that white matter integrity assessed with DTI and erythrocyte membrane omega-3 concentration may provide the means for identifying patients most likely to derive clinical benefit from omega-3 supplementation. To test this hypothesis we will enroll 58 patients with recent-onset schizophrenia into a 4 month long randomized double blind placebo-controlled study of risperidone versus risperidone plus omega-3 supplementation. DTI exams and peripheral omega-3 concentration will be obtained prior to the initiation of treatment and the primary outcome measure will be the total Brief Psychiatric Rating Scale Score. Confirmation of our hypothesis will provide the data required to design a more definitive omega-3 trial using a targeted patient approach with the long-term goal of determining which patients can benefit from omega-3 treatment.